全文获取类型
收费全文 | 18421篇 |
免费 | 46篇 |
国内免费 | 65篇 |
专业分类
系统科学 | 360篇 |
丛书文集 | 445篇 |
教育与普及 | 45篇 |
理论与方法论 | 75篇 |
现状及发展 | 8135篇 |
研究方法 | 854篇 |
综合类 | 8360篇 |
自然研究 | 258篇 |
出版年
2012年 | 286篇 |
2011年 | 604篇 |
2010年 | 125篇 |
2009年 | 101篇 |
2008年 | 342篇 |
2007年 | 416篇 |
2006年 | 362篇 |
2005年 | 401篇 |
2004年 | 372篇 |
2003年 | 412篇 |
2002年 | 340篇 |
2001年 | 624篇 |
2000年 | 622篇 |
1999年 | 362篇 |
1993年 | 91篇 |
1992年 | 346篇 |
1991年 | 260篇 |
1990年 | 306篇 |
1989年 | 275篇 |
1988年 | 269篇 |
1987年 | 279篇 |
1986年 | 289篇 |
1985年 | 347篇 |
1984年 | 246篇 |
1983年 | 224篇 |
1982年 | 209篇 |
1981年 | 240篇 |
1980年 | 262篇 |
1979年 | 574篇 |
1978年 | 466篇 |
1977年 | 473篇 |
1976年 | 354篇 |
1975年 | 376篇 |
1974年 | 586篇 |
1973年 | 455篇 |
1972年 | 416篇 |
1971年 | 511篇 |
1970年 | 658篇 |
1969年 | 574篇 |
1968年 | 493篇 |
1967年 | 529篇 |
1966年 | 441篇 |
1965年 | 332篇 |
1959年 | 199篇 |
1958年 | 295篇 |
1957年 | 195篇 |
1956年 | 173篇 |
1955年 | 168篇 |
1954年 | 159篇 |
1948年 | 87篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
261.
262.
A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma 总被引:1,自引:0,他引:1
Bertolotto C Lesueur F Giuliano S Strub T de Lichy M Bille K Dessen P d'Hayer B Mohamdi H Remenieras A Maubec E de la Fouchardière A Molinié V Vabres P Dalle S Poulalhon N Martin-Denavit T Thomas L Andry-Benzaquen P Dupin N Boitier F Rossi A Perrot JL Labeille B Robert C Escudier B Caron O Brugières L Saule S Gardie B Gad S Richard S Couturier J Teh BT Ghiorzo P Pastorino L Puig S Badenas C Olsson H Ingvar C Rouleau E Lidereau R Bahadoran P Vielh P Corda E Blanché H Zelenika D 《Nature》2011,480(7375):94-98
263.
264.
Huang PY Ruiz-Vargas CS van der Zande AM Whitney WS Levendorf MP Kevek JW Garg S Alden JS Hustedt CJ Zhu Y Park J McEuen PL Muller DA 《Nature》2011,469(7330):389-392
The properties of polycrystalline materials are often dominated by the size of their grains and by the atomic structure of their grain boundaries. These effects should be especially pronounced in two-dimensional materials, where even a line defect can divide and disrupt a crystal. These issues take on practical significance in graphene, which is a hexagonal, two-dimensional crystal of carbon atoms. Single-atom-thick graphene sheets can now be produced by chemical vapour deposition on scales of up to metres, making their polycrystallinity almost unavoidable. Theoretically, graphene grain boundaries are predicted to have distinct electronic, magnetic, chemical and mechanical properties that strongly depend on their atomic arrangement. Yet because of the five-order-of-magnitude size difference between grains and the atoms at grain boundaries, few experiments have fully explored the graphene grain structure. Here we use a combination of old and new transmission electron microscopy techniques to bridge these length scales. Using atomic-resolution imaging, we determine the location and identity of every atom at a grain boundary and find that different grains stitch together predominantly through pentagon-heptagon pairs. Rather than individually imaging the several billion atoms in each grain, we use diffraction-filtered imaging to rapidly map the location, orientation and shape of several hundred grains and boundaries, where only a handful have been previously reported. The resulting images reveal an unexpectedly small and intricate patchwork of grains connected by tilt boundaries. By correlating grain imaging with scanning probe and transport measurements, we show that these grain boundaries severely weaken the mechanical strength of graphene membranes but do not as drastically alter their electrical properties. These techniques open a new window for studies on the structure, properties and control of grains and grain boundaries in graphene and other two-dimensional materials. 相似文献
265.
Bacterial persistence is a state in which a sub-population of dormant cells, or 'persisters', tolerates antibiotic treatment. Bacterial persisters have been implicated in biofilms and in chronic and recurrent infections. Despite this clinical relevance, there are currently no viable means for eradicating persisters. Here we show that specific metabolic stimuli enable the killing of both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) persisters with aminoglycosides. This potentiation is aminoglycoside-specific, it does not rely on growth resumption and it is effective in both aerobic and anaerobic conditions. It proceeds by the generation of a proton-motive force which facilitates aminoglycoside uptake. Our results demonstrate that persisters, although dormant, are primed for metabolite uptake, central metabolism and respiration. We show that aminoglycosides can be used in combination with specific metabolites to treat E. coli and S. aureus biofilms. Furthermore, we demonstrate that this approach can improve the treatment of chronic infections in a mouse urinary tract infection model. This work establishes a strategy for eradicating bacterial persisters that is based on metabolism, and highlights the importance of the metabolic environment to antibiotic treatment. 相似文献
266.
267.
Rothberg JM Hinz W Rearick TM Schultz J Mileski W Davey M Leamon JH Johnson K Milgrew MJ Edwards M Hoon J Simons JF Marran D Myers JW Davidson JF Branting A Nobile JR Puc BP Light D Clark TA Huber M Branciforte JT Stoner IB Cawley SE Lyons M Fu Y Homer N Sedova M Miao X Reed B Sabina J Feierstein E Schorn M Alanjary M Dimalanta E Dressman D Kasinskas R Sokolsky T Fidanza JA Namsaraev E McKernan KJ Williams A Roth GT Bustillo J 《Nature》2011,475(7356):348-352
The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome. 相似文献
268.
269.
270.
Zaidi MR Davis S Noonan FP Graff-Cherry C Hawley TS Walker RL Feigenbaum L Fuchs E Lyakh L Young HA Hornyak TJ Arnheiter H Trinchieri G Meltzer PS De Fabo EC Merlino G 《Nature》2011,469(7331):548-553
Cutaneous malignant melanoma is a highly aggressive and frequently chemoresistant cancer, the incidence of which continues to rise. Epidemiological studies show that the major aetiological melanoma risk factor is ultraviolet (UV) solar radiation, with the highest risk associated with intermittent burning doses, especially during childhood. We have experimentally validated these epidemiological findings using the hepatocyte growth factor/scatter factor transgenic mouse model, which develops lesions in stages highly reminiscent of human melanoma with respect to biological, genetic and aetiological criteria, but only when irradiated as neonatal pups with UVB, not UVA. However, the mechanisms underlying UVB-initiated, neonatal-specific melanomagenesis remain largely unknown. Here we introduce a mouse model permitting fluorescence-aided melanocyte imaging and isolation following in vivo UV irradiation. We use expression profiling to show that activated neonatal skin melanocytes isolated following a melanomagenic UVB dose bear a distinct, persistent interferon response signature, including genes associated with immunoevasion. UVB-induced melanocyte activation, characterized by aberrant growth and migration, was abolished by antibody-mediated systemic blockade of interferon-γ (IFN-γ), but not type-I interferons. IFN-γ was produced by macrophages recruited to neonatal skin by UVB-induced ligands to the chemokine receptor Ccr2. Admixed recruited skin macrophages enhanced transplanted melanoma growth by inhibiting apoptosis; notably, IFN-γ blockade abolished macrophage-enhanced melanoma growth and survival. IFN-γ-producing macrophages were also identified in 70% of human melanomas examined. Our data reveal an unanticipated role for IFN-γ in promoting melanocytic cell survival/immunoevasion, identifying a novel candidate therapeutic target for a subset of melanoma patients. 相似文献